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. 2022 Dec 22;22(1):1343.
doi: 10.1186/s12885-022-10325-9.

Real-world patient-reported outcomes and physician satisfaction with poly (ADP-ribose) polymerase inhibitors versus chemotherapy in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative advanced breast cancer from the United States, Europe, and Israel

Reshma Mahtani  1 , Alexander Niyazov  2 , Bhakti Arondekar  3 , Katie Lewis  4 , Alex Rider  4 , Lucy Massey  4 , Michael Patrick Lux  5
Affiliations

Real-world patient-reported outcomes and physician satisfaction with poly (ADP-ribose) polymerase inhibitors versus chemotherapy in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative advanced breast cancer from the United States, Europe, and Israel

Reshma Mahtani et al. BMC Cancer. .

Abstract

Background: In clinical trials, poly (ADP-ribose) polymerase inhibitors (PARPi) versus chemotherapy resulted in significantly improved progression-free survival, manageable adverse event profiles, and favorable patient-reported outcomes (PROs) in patients with human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) and germline BRCA1/2 mutations (gBRCA1/2mut). The objective of this study was to evaluate PROs and physician satisfaction with treatment in patients with gBRCA1/2mut HER2- ABC receiving PARPi or physician's choice of chemotherapy in a multi-country, real-world setting.

Methods: This retrospective analysis used data from the Adelphi Real World ABC Disease Specific Programmes in the United States, European Union, and Israel. PROs were assessed at a single timepoint using the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) scale, Cancer Therapy Satisfaction Questionnaire (CTSQ), and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) and the breast cancer-specific module (QLQ-BR23). Baseline PROs were not assessed. Physician satisfaction with treatment scores was dichotomized to a 0/1 variable (0 = very dissatisfied/dissatisfied/moderately satisfied; 1 = satisfied/very satisfied). Scores were compared using inverse-probability-weighted regression adjustment, controlling for multiple confounding factors.

Results: The study included 96 patients (PARPi, n = 38; platinum/non-platinum-based chemotherapy, n = 58). Patients receiving PARPi versus chemotherapy reported significantly better scores on the EQ-5D-5L Health Utility Index. On the EORTC QLQ-C30 functional scales, patients receiving PARPi reported significantly better scores (mean ± SE) for physical functioning (80.0 ± 2.4 vs 71.9 ± 3.4; p < 0.05) and social functioning (82.0 ± 6.2 vs 63.6 ± 3.7; p < 0.05) and, on the symptom scales, reported significantly better scores for constipation (1.9 ± 1.8 vs 18.7 ± 3.2; p < 0.001), breast symptoms (0.4 ± 3.9 vs 13.3 ± 2.6; p < 0.01), arm symptoms (2.6 ± 1.3 vs 11.4 ± 2.4; p = 0.001), and systemic therapy side effects (13.5 ± 1.8 vs 29.4 ± 2.3; p < 0.001). In contrast, patients receiving chemotherapy scored significantly better on the nausea/vomiting scale (18.3 ± 2.8 vs 34.5 ± 5.1; p < 0.01). Patients receiving PARPi reported numerically better satisfaction scores on the CTSQ scales. Physicians were more likely to be satisfied/very satisfied with PARPi versus chemotherapy (95.4% ± 7.3% vs 40.8% ± 6.2%; p < 0.001).

Conclusions: The PRO findings in this real-world population of patients with gBRCA1/2mut HER2- ABC complement those from the pivotal clinical trials, providing further support for treatment with PARPi in these patients.

Keywords: Advanced breast cancer; BRCA1/2 mutation; Chemotherapy; Patient-reported outcomes; Poly (ADP-ribose) polymerase inhibitors; Quality of life; Real-world.

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Conflict of interest statement

RM has acted as consultant for Agendia, Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Genentech, Gilead, Hologic, Eli Lilly, Merck, Novartis, Pfizer, Puma, Sanofi, and SeaGen; and has contracted research for AstraZeneca, Genentech, and Veru.

AN, BA are employees of and own stock in Pfizer Inc.

KL, AR, and LM are employees of Adelphi Real World.

MPL has received honoraria for lectures, consulting, and/or working in an advisory role for Eli Lilly, AstraZeneca, MSD, Novartis, Pfizer, Eisai, Exact Sciences, Daiichi-Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Onkowissen, and Roche; received fees for travel, accommodations, and/or expenses from Roche and Pfizer; acted as editorial board member of Medac; and received fees for non-CME services from Eli Lilly, Roche, MSD, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Gilead, Grünenthal, AstraZeneca, and Eisai.

Figures

Fig. 1
Fig. 1
BRCA1/2-Mutation Status Testing. ABC, advanced breast cancer; BRCA1/2, breast cancer susceptibility gene 1 or 2; HER2–, human epidermal growth factor receptor 2–negative; IPWRA, inverse-probability–weighted regression adjustment. *Includes: not tested; not known to have a BRCA1/2 germline mutation test result; not known to have BRCA1/2 germline and somatic wildtype test results. †Of the total population of 3036 patients, 1239 agreed to participate in the patient-reported outcomes analysis. ‡Patients had all patient-reported outcome and covariate data available for the IPWRA analysis
Fig. 2
Fig. 2
IPWRA Analysis for EQ-5D Health Utility. Mean EQ-5D Summary Index. EQ-5D, EuroQoL-5 Dimension; IPWRA, inverse-probability–weighted regression adjustment; PARPi, poly (ADP-ribose) polymerase inhibitors. Bold P values represent those that are statistically significant (p < 0.05). *Includes platinum- and non–platinum-based regimens. Error bars represent standard error
Fig. 3
Fig. 3
IPWRA Analysis for the EORTC QLQ-C30 and EORTC QLQ-BR23a GHS/QoL, Functional Scales, and Symptom Scales. Mean GHS/QoL and functional scales (A) and symptoms scale (B) scores adjusted for patient demographic and clinical variables by IPWRA for patients treated with PARPi and chemotherapy. EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Core 30; EORTC QLQ-BR23, European Organisation for Research and Treatment of Cancer Quality of Life Breast Cancer module; GHS/QoL, global health status/quality of life; IPWRA, inverse-probability–weighted regression adjustment; PARPi, poly (ADP-ribose) polymerase inhibitors. EORTC QLQ-BR23 category Sexual Enjoyment was excluded owing to low sample size. *Includes platinum- and non–platinum-based regimens. Bold P values represent those that are statistically significant (p < 0.05). Error bars represent standard error
Fig. 4
Fig. 4
IPWRA Analysis for CTSQ Scores and Physician Satisfaction with Treatment. Mean scores for 3 CTSQ domains (A) and proportion of physicians satisfied with treatment (B) adjusted for patient demographic and clinical variables by IPWRA for patients treated with PARPi or chemotherapy. CTSQ, Cancer Therapy Satisfaction Questionnaire; IPWRA, inverse-probability–weighted regression adjustment; PARPi, poly (ADP-ribose) polymerase inhibitors. *Includes platinum- and non–platinum-based regimens. Error bars represent standard error
See this image and copyright information in PMC

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